tbuckley/cabot-search huggingface dataset:
Variation of body composition and its impact on survival in a global population of patients receiving multimodal treatment for esophageal cancer.
Authors: Piers R Boshier, Donald E. Low
Journal: Journal of Clinical Oncology (2023)

e16093 Background: Growing evidence has supported a role for body composition in predicting survival in patients undergoing esophagectomy. This study seeks to define baseline variation and clinical correlates of body composition in an international cohort of patients undergoing esophagectomy for cancer. Methods: Patients who underwent esophagectomy in fourteen high-volume centers between January 2007 to December 2019 were eligible for inclusion. Skeletal muscle, visceral and subcutaneous adipose tissues within CT images, acquired at the time of diagnosis, were analyzed by a single trained assessor in accordance with a standardized protocol. Survival status was censored June 2022. Results: In total 1716 patients were recruited to this study from three global regions: North America (n = 386; 22.5%), Europe (n = 940; 54.8%) and Asia (n = 390; 22.7%). Patients were predominantly male (79.5%) and adenocarcinoma was the most common histological subtype (66.6%). Wide variation in skeletal muscle (17.1 to 83.5cm 2 ), visceral (0.2 to 170.1cm 2 ) and subcutaneous adipose tissue (0.2 to 216.8cm2) was observed. Characteristics that were significantly associated with levels of muscle and adiposity were global region, sex, age and histological subtype. Compared to adenocarcinoma, SCC was associated with significantly (p &lt; .0001) lower levels of muscle and adiposity, a finding that was independent of global region, sex, and age using a multivariable linear regression model (p &lt; .0001). Reduced skeletal muscle and an excess of total adiposity at the time of diagnosis was associated with 90-day mortality and worse long-term survival. A nomogram including skeletal muscle, total adiposity at diagnosis and other tumor and patient specific variables was constructed to allow convenient survival prediction. Conclusions: This is the first study to assess parameters of body composition in a global cohort of patients receiving multimodal therapy for esophageal cancer. Findings highlight important regional and disease specific variation in body composition parameters and demonstrate the clinical utility of these measurements in predicting both early and late survival after esophagectomy. Results are intended to inform future guidelines for the use of body composition assessment in routine clinical practice.
Mixed medullary-follicular carcinoma: A national analysis and the demographic features.
Authors: Yanick Tade, Darby Keirns, Beau Hsia, Peter T. Silberstein, Xinxin Wu
Journal: Journal of Clinical Oncology (2023)

e18090 Background: Mixed medullary-follicular carcinoma (MMFC) is a rare malignant type of cancer that affects the thyroid. Unlike other thyroid cancers, MMFC is distinct by its solid-nonfollicular pattern which includes both follicular and C-cell elements. Nearly 70% of patients present with distant metastasis to the lungs, bone, brain and/or liver with a median survival time of 75 months, plus or minus 51 months. Because MMFC is a rare cancer, analyzing the trend in diagnoses can provide important information about its epidemiology. The National Cancer Database (NCDB) was analyzed to determine how patient demographic characteristics affected diagnosis of MMFC. Methods: A retrospective cohort study from 2004 to 2020 was conducted using the NCDB. 153 patients were found with a histologically confirmed diagnosis of MMFC (ICD-8346-3). Gender, race, Hispanic origin, level of education, insurance coverage, type of treatment facility, and distance from facility were analyzed via descriptive statistics and trends in incidence were interpreted using regression analysis. Results: The frequency of patients diagnosed with MMFC has remained consistent since 2004 (R 2 = 0.1) with over 10 diagnoses per year. Of the 153 patients found, the average age of diagnosis was 59.05 years (SD = 14.36, range = 18 – 90 years). Approximately two-thirds of patients were female (62.7%) and the remainder were male (37.3%). Most of the patients were Non-Hispanic White (86.3%) compared to 7.2% of the patients which were of Spanish-hispanic origin. More patients were in the top income quartile (37.3%) than those in the second (18.3%), third (21.6%), or fourth (11.1%) quartiles. The other 11.8% were of unknown income status. The majority of patients were privately insured (52.9%), followed by coverage under Medicare/Medicaid (43.1%). More patients lived in metropolitan counties with a population of 250,000 or more (88.2%) compared to urban or rural areas (11.8%). A large percentage of patients were treated at an academic or comprehensive community cancer program (72.6%) compared to non-academic programs (27.4%). Patients traveled an average of 33.9 miles (SD = 93.90, Range = 0.5 – 806.8) to get to the treatment facility. Conclusions: MMFC remains a rare diagnosis. This study explores a significant gap in existing knowledge on patient characteristics that might present with MMFC. The majority of patients were White, non-Hispanic, insured by private insurance, lived in metropolitan areas, and in the top quartile of income earners. This novel study of socioeconomic factors in MMFC patients suggest that patients diagnosed with this uncommon cancer might have better access to diagnosis. Previous literature on MMFC suggested a predilection for males, but our findings serve as contrary evidence for such preference. As such, additional research to comprehend the role that sex and socioeconomic status might have on MMFC would be valuable.
Urine-based epigenetic profiling for detection of clear cell renal cell carcinoma: A prospective study.
Authors: Wen Kong, Jin Zhang, Hang Dong, Haoran Tang, Pan Du, Shidong Jia
Journal: Journal of Clinical Oncology (2023)

e16545 Background: Clear cell renal cell carcinoma (ccRCC) is a type of kidney cancer that poses a significant challenge in early detection and differentiation from other subtypes in clinical practice. Liquid biopsy using epigenomic signatures represents a potential solution for non-invasive cancer detection and disease surveillance. Methods: In this prospective study, aiming to collect matched tissue-plasma-urine samples from 200 ccRCC patients and 50 non-tumor donors, we enrolled 14 patients with ccRCC and 10 patients with benign kidney lesions. Matched samples (tissue, blood, and urine) were collected and analyzed using the DNA methylation assay, PredicineEPIC. An in-house developed bioinformatics algorithm was used to investigate the genome-wide epigenomic profiles, and a machine-learning model was built for tumor prediction based on tumor-specific methylation patterns. Further enrollment is ongoing. Results: In the exploratory cohort, tissue-based differential methylated regions (DMRs) profiling differentiated tumors from normal renal tissues with high accuracy. The ccRCC-specific methylation patterns were constructed with 637 optimized methylation features, and the machine learning classifier was trained. The prediction efficacy was tested in a larger-scale TCGA-KIRC dataset, which demonstrated high sensitivity and specificity (AUC = 0.985). Compared with the use of blood, urinary cell-free DNA-based methylation profiling allowed for the differentiation of ccRCC patients from healthy controls and patients with benign kidney lesions. Conclusions: The current preliminary study demonstrates the technical feasibility of urine-based methylation study in the identification of patients with ccRCC. Our findings highlight the potential of urine-based methylation profiling in kidney cancer detection and disease surveillance.
Treatment and survival of de novo metastatic hormone sensitive prostate cancer among African American US Veterans.
Authors: Rigoberto De Jesus Pizarro, Robert Bruce Montgomery, Ruth Douglas Etzioni, Kristen Marie Sanfilippo, Saira Khan, Eric Marshall Knoche, Julie Ann Lynch, Martin W. Schoen
Journal: Journal of Clinical Oncology (2023)

5079 Background: Combinations of androgen deprivation therapy (ADT) plus docetaxel (DOC) or androgen signaling inhibitors (ASIs: abiraterone, enzalutamide, etc.) have revolutionized treatment of metastatic hormone sensitive prostate cancer (mHSPC), particularly for high volume disease. However, little is known about the use of and outcomes of combination therapy in African Americans (AA) with de novo mHSPC, due to their lack of representation in clinical studies. This study evaluates the patient characteristics, treatment, and survival in a cohort of US veterans with mHSPC with equal access to treatment under the Veterans Affairs Health System (VA). Methods: Veterans with mHSPC were identified from 2014-2022 in the VA using the initial pathological diagnosis of prostate cancer with SEER stage ‘distant’ and first ADT initiated within 1 month prior and 3 months after diagnosis. Therapies including DOC or ASIs were collected if initiated from 1 month prior to 4 months after ADT. Additional information at the time of diagnosis was collected including Prostate Specific Antigen (PSA), race from VA enrollment, and Charlson Comorbidity Index (CCI). Median survival was obtained for each group and stratified by PSA level &gt;100 ng/mL. Chi-square and ANOVA testing were used differences in survival (OS) were assessed by log-rank testing. Results: 4,248 veterans with de novo mHSPC were identified, 1138 (26.8%) were AA and 3110 (73.2%) white. Black veterans were younger (70.8 vs. 74.8, p&lt;0.001) and had higher median PSA (183 vs. 86.3, p&lt;0.001) with similar mean CCI (4.4 vs. 4.4, p=0.78). AA veterans were likely to have a PSA &gt;100 ng/mL at diagnosis (61.6% vs. 46.1%, p&lt;0.001) and to receive combination therapy than white veterans (36.8% vs. 32.7%, p=0.01). The median OS among AA and white veterans was similar (32.5 months vs. 32.1, p=0.75). In 2,120 veterans with PSA&gt;100 ng/mL (a surrogate for higher volume disease), AA veterans were more likely to receive combination therapy (39.5% vs. 32.9%, p=0.003) without differences in survival in AA veterans compared to white (31.0 vs. 26.9 months, p=0.18). Conclusions: In an equal access health care system, AA veterans had similar survival to white veterans despite having double the PSA levels, reflecting higher risk disease. AA presented 4 years younger and are likely treated with doublet therapy. The differences in the age of onset and burden of disease highlight persistent differences in populations with mHSPC. Further investigations to understand environmental, social, and tumor factors are warranted to explain these disparities. [Table: see text]
Biomarkers of response to first-line nivolumab therapy in patients with advanced renal cell carcinoma (RCC) enrolled in the HCRN GU16-260 trial.
Authors: Nourhan El Ahmar, Sayed Matar, Opeyemi Jegede, Varunika Savla, Aseman Bagheri Sheshdeh, Fatme Ghandour, Thomas Denize, Destiny West, Toni K. Choueiri, Paul J. Catalano, David A. Braun, Naomi B. Haas, Hans J. Hammers, Mehmet Asim Bilen, Mark N. Stein, Jeffrey A. Sosman, Catherine J. Wu, David F. McDermott, Michael B. Atkins, Sabina Signoretti
Journal: Journal of Clinical Oncology (2023)

4549 Background: The HCRN GU16-260 study showed that nivolumab (nivo) monotherapy is active in treatment-naïve patients (pts) with RCC. Although efficacy correlated with tumor cell (TC) PD-L1 expression, more clinically relevant biomarkers are needed. We previously showed that levels of CD8+ tumor-infiltrating lymphocytes (TIL) expressing PD-1 but not TIM-3 and LAG-3 (CD8+ PD1+ TIM3- LAG3-) were associated with response to nivo in previously treated clear cell RCC (ccRCC) pts (Pignon, 2019; Ficial, 2021). Here, we sought to validate these findings in the first-line setting. Methods: Primary tumor tissues from pts with ccRCC (n= 67) and non-ccRCC (n= 13) were analyzed by multiparametric immunofluorescence (IF), and the density of CD8+PD-1+TIM-3-LAG-3- TIL was quantified by image analysis. The correlation of the log-transformed biomarkers with objective response rate (ORR) and progression-free survival (PFS) was assessed in the ccRCC cohort and the combined (ccRCC + non-ccRCC) cohort (n=80) using Cox or logistic regression analysis, or Chi-square/Fisher’s exact test (as appropriate) for statistical inference – alpha level was set at 5% (1-sided). Results: In both the ccRCC and the combined cohort, density of CD8+PD-1+TIM-3-LAG-3- TIL (IF biomarker) measured as continuous variable was associated with ORR (ccRCC: OR = 1.54, p = 0.017; combined: OR = 1.35, p = 0.040) and PFS (ccRCC: HR = 0.79, p = 0.015; combined: HR = 0.85, p = 0.016). At a cutoff optimized for maximum sensitivity for ORR, ccRCC patients with a high (61/67) vs low (6/67) IF biomarker had higher ORR (44.3% vs. 0% p = 0.039) and longer median PFS (10.9 months vs. 4.2 months, p = 0.016). Of note, when combined with the IF biomarker, TC PD-L1 expression (≥1%) further separated the clinical outcomes of ccRCC pts. Conclusions: High levels of CD8+ PD1+ TIM-3-LAG-3- TILs were associated with response to first-line nivo in pts with advanced RCC and the combination with TC PD-L1 status further separated the outcomes of pts with ccRCC, validating our previous findings. Further investigations into the role of myeloid inflammation as determinant of clinical outcome to nivo therapy are ongoing. Clinical trial information: NCT03117309 . [Table: see text]
Adjuvant everolimus in patients (Pts) with localized non-clear cell renal cell carcinoma (RCC): Subgroup analysis from the Everest trial (SWOG S0931).
Authors: Shuchi Gulati, Catherine Tangen, Christopher W. Ryan, Ulka N. Vaishampayan, Brian M. Shuch, Pedro C. Barata, Deepak K Pruthi, Cristiane Decat Bergerot, Abhishek Tripathi, Ian M Thompson, Primo N Lara, Sumanta Kumar Pal
Journal: Journal of Clinical Oncology (2023)

4546 Background: In S0931, adjuvant treatment with the mTOR inhibitor everolimus respectively yielded disease-free survival (DFS) and overall survival (OS) hazard ratios (HR) of 0.85 (95% CI 0.71-1.00) and 0.90 (95% CI 0.71-1.13) in pts with resected, localized RCC. Previously, everolimus had been shown to be active in chromophobe RCC (chRCC; Tannir et al Eur Urol 2016) and papillary RCC (papRCC; Escudier et al Eur J Cancer 2016). We sought to evaluate the efficacy of everolimus within these non-clear cell subsets of EVEREST. Methods: 1545 adult pts with treatment-naïve, non-metastatic, fully-resected RCC at intermediate high- (pT1 G3-4 N0 to pT3a G1-2 N0) or very high-risk (pT3a G3-4 to pT4 G-any or N+) for recurrence were randomized 1:1 to 54 weeks of everolimus 10 mg PO daily or placebo within 12 weeks of radical or partial nephrectomy. Exploratory analyses of RFS and OS chromophobe and papillary subgroups were performed. Results: A total of 99 eligible pts had chRCC; 109 had papRCC (16 type I; 37 type II; 56 NOS). Median follow-up is 6.3 years. Pt characteristics were balanced between the 2 arms in each histological group. Thirty-four (34%) pts in the chRCC subgroup and 50 (46%) pts in the papRCC subgroup had very high-risk disease. Fewer pts completed all 54 weeks of everolimus in each subgroup compared to placebo (49% vs. 74% in the ChRCC subgroup and 46% vs. 71% in the papillary subgroup). DFS and OS for each subgroup are shown. Conclusions: Non-clear cell histology accounted for a considerable proportion (~13%) of S0931 pts. The estimated everolimus HRs for DFS and OS in the chRCC subset are consistent with the overall trial result, but those same modest HRs were not seen in papRCC, in contrast to prior reports of mTOR inhibitor activity in this subtype. Although inferences are limited by sample size and wide CIs, this is the largest experience in chRCC or papRCC among any adjuvant trials presented to date. Clinical trial information: NCT01120249 . [Table: see text]
Cell-free urinary tumor DNA to detect minimal residual disease prior to repeat-transurethral resection of bladder tumor in non-muscle invasive bladder cancer: A prospective study.
Authors: Kyle M. Rose, Prithvi Murthy, Billie Gould, Heather L. Huelster, Facundo Davaro, Lucia P. Camperlengo, Pan Du, Shidong Jia, Aram Vosoughi, G. Daniel Grass, Philippe E. Spiess, Scott Michael Gilbert, Wade J. Sexton, Roger Li
Journal: Journal of Clinical Oncology (2023)

e16598 Background: Cell-free urinary tumor DNA (utDNA) generated from tumor genomic sequencing is an emerging biomarker showing tremendous potential for detecting minimal residual disease (MRD) in muscle-invasive and metastatic bladder cancer. We performed a prospective study to assess utDNA’s ability to measure MRD at the time of standard-of-care repeat transurethral resection of bladder tumor (rTURBT) in non-muscle invasive bladder cancer (NMIBC). Methods: Patients with high-risk NMIBC were enrolled prior to rTURBT. Index tumor and rTURBT mutational profile was performed via PredicineWES whole exome sequencing across 20,000 genes. Genes with non-synonymous (NS) mutations observed in index and rTURBT specimens identified in a minimum of two samples are reported. Urine samples were taken immediately prior to r-TURBT. utDNA detection was performed by ultra-deep sequencing of urinary cfDNA using a custom panel of up to 50-baseline mutations per patient together with a fixed core panel covering hotspot regions and actionable variants via PredicineBEACON Urinary tumor fraction was used to call utDNA positivity. The primary endpoint was the detection of utDNA to predict MRD at the time of repeat-TURBT. Results: Eleven patients underwent rTURBT for high risk NMIBC. Residual tumor was detected at rTURBT in 8/11 (73%) patients. Fifty genes with NS mutations found in at least two samples were identified including TP53, PIK3CA, RB1, MYC, CDKN1A and ARID1A. A median of 146 (range 39-418) and 91 NS (range 2-312) mutations were identified in the index and re-TUR specimens, respectively. Concordance rates were 83% on average between primary and rTURBT, highest for patients upstaged to T2 disease, and lowest for patients harboring CIS. Genomic alterations in urinary tumor DNA were detected in ten patients. The tumor fraction of utDNA was higher in patients with residual disease (mean 2.5% vs. 0.2%, p=0.10). Using tumor-fraction to predict MRD, the area under the receiver-operator curve (AUC) for this test was 0.85. Using an optimal threshold of ≥3.3% tumor-fraction to define utDNA positivity, the test had a sensitivity of 75% at 100% specificity. Conclusions: Urinary tumor DNA shows promise as a surrogate for minimal residual disease and may predict TURBT pathology for NMIBC. Genomic alterations between index and rTURBT tumors are highly concordant in papillary tumors even in the setting of upstaging, which may aid in targeted intravesical or systemic therapy selection. Larger cohorts and long-term follow up is needed to determine if utDNA can risk-stratify patients prior to rTURBT and predict long-term recurrence.
The sit to stand test in cancer patients and survivors.
Authors: Adrian Cristian
Journal: Journal of Clinical Oncology (2023)

e24058 Background: The sit to stand test in 30 seconds has been used to measure power, strength, endurance, and balance. It has also been described as a useful tool in identifying presence of sarcopenia. Methods: Retrospective chart review of cancer patients and survivors referred to cancer rehabilitation clinic over a 5-year period from 1/1/2018-12/31/2022 at a large cancer institute in the southeastern part of the United States. Patients were assessed at their initial evaluation using the sit to stand test in 30 seconds (STS-30). Scoring for the sit to stand score was divided into 2 groups (impaired and good scores) based on age and gender specific normative data. Data was also collected for patients/survivors with different body mass index (BMI) ranges: underweight: (BMI &lt; 18.5); normal weight (BMI 18.5-24.99); overweight (BMI: 25.-29.99), obese ( &gt; 30) as well as stages of cancer (stage 0-4). Results: 1406 cancer patients and survivors underwent STS-30 at their initial evaluation in cancer rehabilitation clinic. This included cancers of breast, GI, GU, lung, gynecologic, brain/spine, hematologic, head and neck, musculoskeletal, endocrine and skin. 749/1406 (53.27%) had impaired STS-30 with an average score of 6.45 repetitions in 30 seconds and 657/1406 (46.73%) had good scores with an average of 14.75 repetitions in 30 seconds. BMI and STS-30: 1,298 patients had BMI data available. 912/1298 (70.3%) were overweight or obese. 501/912 (54.93%) had an impaired STS-30 with an average of 6.76 repetitions in 30 seconds. 411/912 (45.07%) had a good STS-30 with an average of 14.66 repetitions in 30 seconds. 386/1298 (29.7%) had a normal BMI or were underweight. 173/386 (44.82%) had an impaired STS-30 with an average of 6.57 repetitions in 30 seconds. 213/386 (55.18%) had a good STS-30 with an average of 15.06 repetitions in 30 seconds. Stage of cancer and STS-30: The stage of cancer was known for 647 patients/survivors. 462/647 (71.4%) had stage 0-3 cancer. 218/462 (47.2%) had an impaired STS-30 with an average of 6.91 repetitions in 30 seconds.244/462(52.8%) of them had a good STS-30 with an average of 14.54 repetitions in 30 seconds. 185/647 (28.6%) had stage 4 cancer. 114/185 (61.62%) had an impaired STS-30 with an average of 6.04 repetitions in 30 seconds. 71/185 (38.38%) had a good STS-30 score with an average of 14.27 repetitions in 30 seconds. Conclusions: The STS-30 was impaired in a significant percentage of cancer patients and survivors across all stages, implying the possible presence of sarcopenia in this population. Stage 4 cancer patients and overweight/obese patients were at especially high risk of having an impaired STS-30. Clinicians should utilize the STS-30 to screen cancer patients and survivors and if scores are impaired, further assess for presence of sarcopenia and introduce interventions to address it.